Novel sulfonamide porphyrin TBPoS-2OH used in photodynamic therapy for malignant melanoma - 19/12/20
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Highlights |
• | The TBPoS-2OH has photo-cytotoxicity and can effectively inhibit melanoma cell proliferation with a LD50 in the nM range. |
• | After entering the lysosome, TBPO-2OH activated the mitochondrial apoptosis pathway under the stimulation of light. |
• | TBPoS-2OH increases the level of reactive oxygen species in melanoma cells after photo-irradiation. |
Abstract |
The application of photodynamic therapy (PDT) for the treatment of skin diseases has been receiving much attention. Here, we examined the anti-tumor effect of a novel porphyrin-based photosensitizer TBPoS-2OH in the malignant melanoma A375 and B16 cells. TBPoS-2OH has obvious cell photo-cytotoxicity, but it has low cell dark-cytotoxicity. Further research showed that TBPoS-2OH is enriched in lysosomes after being taken up by cells. Subsequently, the apoptotic rates were significantly increased in TBPoS-2OH-treated A375 and B16 cells. The specific mechanism may be that after receiving light stimulation, TBPoS-2OH could effectively increase the level of intracellular reactive oxygen species (ROS), thereby activating mitochondrial apoptosis pathway-related proteins in A375 and B16 cells. We found an increase in the content of cytochrome C in the cytoplasm, and the levels of related proteins, such as cleaved caspase-3, cleaved caspase-9, and cleaved PARP1, were significantly increased in TBPoS-2OH-treated cells. These results indicated that the new compound TBPoS-2OH could be developed and become an alternative drug for the treatment of melanoma. Some reference ideas for the development of new photosensitizers are also provided.
Le texte complet de cet article est disponible en PDF.Keywords : Photodynamic therapy, Porphycene, Mitochondria-mediated apoptosis, ROS, Tumor, Melanoma
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Vol 133
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